PMID- 27401639 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181202 IS - 1976-2437 (Electronic) IS - 0513-5796 (Print) IS - 0513-5796 (Linking) VI - 57 IP - 5 DP - 2016 Sep TI - Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model. PG - 1095-105 LID - 10.3349/ymj.2016.57.5.1095 [doi] AB - PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-alpha n=5] using a Cricket Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-alpha groups, compared to the oil or saline group (82.1+/-5.1% and 94.6+/-2.2% compared to 49.6+/-14.0% and 46.5+/-9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-alpha group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis. FAU - Kim, Jung Sun AU - Kim JS AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Lee, Seul Gee AU - Lee SG AD - Graduate Program in Science for Aging, Yonsei University, Seoul, Korea. FAU - Oh, Jaewon AU - Oh J AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Park, Sungha AU - Park S AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. shpark0530@yuhs.ac. FAU - Park, Se Il AU - Park SI AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. FAU - Hong, Sung Yu AU - Hong SY AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Sehoon AU - Kim S AD - Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. FAU - Lee, Sang Hak AU - Lee SH AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Ko, Young Guk AU - Ko YG AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Choi, Donghoon AU - Choi D AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Hong, Myeong Ki AU - Hong MK AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. AD - Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Jang, Yangsoo AU - Jang Y AD - Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea. AD - Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. AD - Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PL - Korea (South) TA - Yonsei Med J JT - Yonsei medical journal JID - 0414003 RN - 0 (Cholesterol, Dietary) RN - 0 (HMGB1 Protein) RN - 0 (Olive Oil) RN - 0 (Tumor Necrosis Factor-alpha) RN - 451W47IQ8X (Sodium Chloride) SB - IM MH - Animals MH - Cholesterol, Dietary/administration & dosage MH - *Disease Models, Animal MH - Endothelium/surgery MH - HMGB1 Protein/*adverse effects MH - Iliac Artery/diagnostic imaging/pathology/surgery MH - Injections, Intra-Arterial MH - Macrophages MH - Male MH - Olive Oil/adverse effects MH - Plaque, Atherosclerotic/*chemically induced/diagnostic imaging/pathology MH - Rabbits MH - Sodium Chloride/adverse effects MH - Tomography, Optical Coherence MH - Tumor Necrosis Factor-alpha/*adverse effects PMC - PMC4960374 OTO - NOTNLM OT - Rabbit model OT - atherosclerosis OT - balloon injury OT - inflammatory protein COIS- The authors have no financial conflicts of interest. EDAT- 2016/07/13 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/09/01 CRDT- 2016/07/13 06:00 PHST- 2015/12/07 00:00 [received] PHST- 2016/02/09 00:00 [revised] PHST- 2016/03/03 00:00 [accepted] PHST- 2016/07/13 06:00 [entrez] PHST- 2016/07/13 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/09/01 00:00 [pmc-release] AID - 57.1095 [pii] AID - 10.3349/ymj.2016.57.5.1095 [doi] PST - ppublish SO - Yonsei Med J. 2016 Sep;57(5):1095-105. doi: 10.3349/ymj.2016.57.5.1095.